Primary Development Of Multi-parameter Feedback Regulation And Control System For Crystallization

Crystallization is a key unit operation for product separation and purification. According tothe demand of modern society, the development of modern chemical production graduallyfocus on high value-added chemical products, the traditional trial-and-error method losesefficiency, economy and flexibility for crystallization. In this paper, process analysistechnologies (PAT) were utilized in the primary development of multi-parameter feedbackregulation and control system for crystallization, which are based on the concept of Qualityby Design (QbD).The system consists of the following parts:(1) a ATR-UV spectroscopy,(2) aturbidity meter,(3) a pt100,(4) a program Control Thermostat and (5) a glass vessel, etc.Functional module for the measurement of metastable zone width (MSZW), which based onin situ monitoring of solution concentration and supersaturation, was successfully developed.The reliability of MSZW monitoring module was verified by the experiment of paracetamolin ethanol. The method for in situ measurement of solution concentration was developedbased on ATR-UV spectroscopy coupled with PLS chemometric technique under the fullyconsideration of temperature and concentration effect on ATR-UV spectroscopy. The accuracyof online monitoring model was verified through the gravimetric method with a RMSEP of0.75%.Combined with FBRM, the developed system for crystallization was used forcontrastive analysis of the effect of natural cooling, linear cooling and controlled coolingpolicy on crystallization. Based on the in situ measurement and analysis of critical parametersduring cooling crystallization, e.g. solution temperature, concentration, supersaturation andcrystal size distribution, it’s found that the outbreak of nucleation exists in both naturalcooling crystallization and linear cooling crystallization, and the controlled cooling policy hasbetter performance for the cooling crystallization.The developed system is a preliminary attempt for the control of crystallization, whichwould have favorable application prospect after subsequent improvement.